Various 7.beta.-amino cephalosporins and 6.beta.-amino penicillins including those having a 7.alpha.- or 6.alpha.-methoxy substituents are employed as starting materials in the preparation of semi-synthetic cephalosporins and penicillins. These 7.beta.-amino cephalosporins and 6.beta.-amino penicillins are for economic reasons prepared by removing the acyl sidechain from cephalosporins and penicillins that are obtained by fermentation processes. Both chemical and enzymatic processes have been employed to accomplish this deacylation.
For example Weissenburger et al. U.S. Pat. Nos. 3,499,909 and 3,575,970 disclose deacylation processes in which the acylated penicillin or cephalosporin is converted to a silyl ester, halogenated to form an iminohalide, reacted with an alcohol to form an iminoether, and then treated with water and a hydroxyl containing compound to remove the acyl sidechain.
Chauvette in U.S. Pat. No. 3,549,628 discloses preparing 7-ADCA by converting an acylated 7-ADCA ester to its iminohalide, treating with alcohol to form the iminoether, and hydrating to remove the acyl sidechain. Hayes et al. in U.S. Pat. No. 3,840,532 disclose a similar process in which particular solvent systems are employed.
Johnson et al. in U.S. Pat. Nos. 3,573,295 and 3,573,296 disclose process for removing the acyl sidechain from cephaloporin C which involve a silyl ester, halogenating, converting the iminohalide to an iminoether, and hydrolyzing. Johnson et al. in U.S. Pat. No. 3,932,392 disclose a deacylation process employing particular acid scavengers during the halogenating step.
Fechting et al. in U.S. Pat. Nos. 3,697,515 and 3,875,151 and Bickel et al. in U.S. Pat. No. 3,920,638 disclose deacylation processes which involve forming an iminohalide, converting the iminohalide to an iminoether, and hydrolyzing to remove the acyl sidechain.
Karady et al. in U.S. Pat. No. 4,031,086 and Tetrahedron Letters, No. 5, p. 407-408 (1978) disclose a process for chemically removing an acyl sidechain from a cephamycin type cephalosporin.
Lunn et al., Tetrahedron Letters, No. 14, p. 1307-1310 (1974), also disclose a process for chemically removing an acyl sidechain from a cephamycin type cephalosporin.
Tedeka in Belgian Patent No. 788,750 disclose a deacylation process wherein the cephalosporin is converted into an iminohalide, then treated to convert the iminohalide to a thioether, and then treated to remove the acyl sidechain.
Tsushima et al. in U.S. Pat. No. 4,068,071 describe a process for removing the acyl sidechain from penicillins and cephalosporins by first thioacylating, converting the thioacyl compound to a disulfide, and then removing the sidechain by solvolyzation. Tsushima et al. in U.S. Pat. No. 4,068,072 remove the acyl sidechain by converting the thioacyl derivative to a thiohalide and then removing the sidechain by solvolyzation.
Busko-Oszczapowicz et al., Roczniki Chemii Ann. Soc. Chim. Polonorum, Vol. 48, p. 253-261 (1974), disclose converting an acylated iminohalide penicillin to a diacyl penicillin followed by treatment with sodium thiophenolate to remove one of the acyl groups.
Shimizu et al., Chem. Pharm. Bull., Vol. 24, p. 2629-2636 (1976), disclose a selective deacylation process for cephamycin type cephalosporins.
Shiozaki et al., J.C.S. Chem. Comm.; p. 517-518 (1978) disclose a process for removing the acyl sidechain from cephamycin C.